tbuckley/cabot-search huggingface dataset:
Abstract 4263: Autophagic ovarian cancer cells exhibit substantially enhanced sensitivity to ALK inhibition
Authors: Alicia M. Blessing, Weiqun Mao, Lan Pang, Philip Rask, Zhen Lu, Robert C. Bast
Journal: Cancer Research (2019)

Abstract One of the major factors contributing to poor outcomes for patients with ovarian cancer is the persistence of dormant, drug resistant cancer cells after primary surgery and chemotherapy. The persistent cancer found in positive second look operations is poorly vascularized and autophagy is widespread in more than 80% of cases. Consequently, drugs that regulate survival in autophagic cancer cells may be much more active when administered as maintenance therapy than when used to treat gross recurrent disease. Using unbiased siRNA screens, we have identified target genes that regulate the survival of ovarian cancer cells that are undergoing autophagy-induced by the re-expression of DIRAS3 (ARHI) or by serum starvation. Knockdown of the anaplastic lymphoma kinase (ALK) significantly reduced survival of ovarian cancer cells that were undergoing autophagy. Importantly, FDA-approved ALK inhibitors, including crizotinib, exhibited significantly greater toxicity after induction of autophagy by upregulation of DIRAS3 or serum starvation in 5 ovarian cancer cell lines. Induction of autophagy by upregulation of DIRAS3 or serum starvation in ovarian cancer cells reduced the IC50 of crizotinib and other ALK inhibitors ranging from 1.5 to 20-fold (all p-values &amp;lt;0.05). Crizotinib treatment in autophagic cancer cells enhanced autophagy and apoptosis via a decrease in p-STAT3 and BCL-2 signaling. Selective targeting of p-STAT3 or BCL-2 also resulted in significantly greater toxicity after induction of autophagy by upregulation of DIRAS3 or serum starvation in multiple ovarian cancer cells. Inducible upregulation of DIRAS3 by doxycycline in the first 6 weeks prompted autophagy and dormancy in two separate xenograft models (SKOV3 and OVCAR8). Crizotinib treatment of dormant autophagic SKOV3 xenografts prolonged median survival by 9.7 weeks (p&amp;lt;0.0032) and cured a subset of mice. Thirteen of fifteen mice (87%) bearing SKOV3 xenografts and nine of eleven mice (82%) bearing OVCAR8 xenografts, were tumor free at 200 days compared to the other three control arms (overall survival, p&amp;lt;0.0001 and p&amp;lt;0.05, respectively). Our studies suggest that ALK inhibitors might provide an effective agent to eliminate autophagic, dormant, drug resistant ovarian cancer cells that remain after conventional cytoreductive surgery and combination chemotherapy. Citation Format: Alicia M. Blessing, Weiqun Mao, Lan Pang, Philip Rask, Zhen Lu, Robert C. Bast. Autophagic ovarian cancer cells exhibit substantially enhanced sensitivity to ALK inhibition [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4263.
Impressions of cogwheel. General practitioner.
Journal: BMJ (1972)

11 NOVEMBER 1972 t1on about less common disorders with which the clinician can supplemelit his own personal experience.It can in this respect make available to the junior clinician a level of clinical experience which might take him years to accumulate.We ourselves plan experiments which evaluate this particular hypothesis further in respect of disorders of the large bowel.'We are grateful to Professor J. C Goligher for his encouragement and advice during the conduct of this study, and to Pro- fessor Goligher and Mr. D. Johnson for permission to study patients admitted under their care.We are also most grateful to Professor K. Smith and Professor M. Wells, together with the staff of the Department of Computational Science and the
Myocardial Temperatures During Electrical Defibrillation of the Heart
Journal: JAMA (1963)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
1098-83 Gender- and age-related differences in the prognostic value of C-reactive protein in patients with angiographic coronary artery disease
Authors: Lillian L Khor, Joseph B Muhlestein, John F Carlquist, Benjamin D Horne, Tami L Bair, Jeffrey L Anderson, Chloe A Allen Maycock
Journal: Journal of the American College of Cardiology (2004)
Our surgical heritage.
Journal: JAMA (1963)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Johns Hopkins Medical Journal, Baltimore
Journal: JAMA (1970)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Use of chaperones in general practice
Journal: BMJ (2005)

with the findings of Hill et al and Devereaux et al might reflect the difference in response rate, criteria for adequate concealment, recentness of the included trials, or the strategies for contacting and phrasing the questions to the investigators.It is prudent to assume that a notable fraction of the overestimation of the treatment effect associated with unclear allocation concealment is caused by selection bias.This fraction can be reduced through several mechanisms.Journals should endorse and enforce the consolidated standards of reporting trials statement (www.consort-statement.org),which recommends explicit description of the allocation procedures in publications of trials, and the gatekeepers who sanction protocols for funding and approval should demand that adequate methods are described in protocols and implemented in trials.Furthermore, our study adds to the argument that protocols should be made publicly available, 9 18 19 because public access would increase the reliability of critical appraisal of the fraction of trials where the protocol does describe methods for allocation concealment.We thank the scientific and ethical committees for Copenhagen and Frederiksberg, who provided access to the trial protocols and offered administrative support; the researchers who responded to the questionnaires; and J Hedegaard for secretarial support.
<i>JAMA Cardiology</i>
Authors: Robert O. Bonow, Thomas J. Easley, Howard Bauchner
Journal: JAMA (2015)

Cardiovascular disease remains the leading cause of death and disability worldwide, in developed and developing countries. 1-3 Despite the success in the last decade in reducing heart diseaserelated mortality in many countries, with aging of the population and persistent cardiovascular risk factors, the burden of hypertension, ischemic heart disease, heart failure, stroke, valvular heart disease, and atrial fibrillation is reaching epidemic proportions worldwide.Against this global burden, cardiovascular medicine continues to advance rapidly.New drugs, like the PCSK9 inhibitors for hypercholesterolemia and sacubitril for heart failure, and new technological advances, like transcatheter aortic valve replacement, offer the promise of improving care, outcomes, and quality of life for patients with and at risk for cardiovascular disease.Understanding of the morbidity associated with undiagnosed conditions, such as hypertension and atrial fibrillation, is beginning to emerge, and new insights into treatment goals and new technologies and devices provide opportunities for earlier identification and intervention for patients with cardiovascular disease. 4,5The anticipated benefit from stem-cell and other regenerative therapies remains unrealized, but promising research continues. 6,7Yet at the same time, the marked increases in obesity and diabetes, coupled with changing nutritional and lifestyle patterns worldwide, are likely to exacerbate the ongoing cardiovascular disease epidemic.Moreover, cardiovascular medicine is not without its controversies.For the past few years, the "statin debates" have raged on both sides of the Atlantic. 8,9Targets for preventive therapies, the appropriate use of expensive new therapies such as PCSK9 inhibitors, indications for transcatheter aortic valve replacement among elderly patients with advanced comorbidities as well as among patients at low surgical risk, and the role of the polypill in global risk reduction all remain controversial topics.With these and other important issues in mind, JAMA and The JAMA Network are pleased to announce the addition of a new journal-JAMA Cardiology-to our network of journals.The inaugural issue of the journal will be published in early 2016 and will include major research investigations, informative reviews, schol-
This Week in &lt;EMPH TYPE="ITAL"&gt;JAMA&lt;/EMPH&gt;
Authors: Annette Flanagin, Thomas Cole
Journal: JAMA (2004)

An estimated 300 000 children and adolescents serve in rebel armies and government forces, many of whom were abducted and forced to enlist.Efforts are under way to help reintegrate child soldiers into their families and communities.
Inefficient establishment of KSHV latency suggests an additional role for continued lytic replication in Kaposi sarcoma pathogenesis
Authors: Adam Grundhoff, Don Ganem
Journal: Journal of Clinical Investigation (2004)

Kaposi sarcoma–associated (KS-associated) herpesvirus (KSHV) infection is linked to the development of both KS and several lymphoproliferative diseases. In all cases, the resulting tumor cells predominantly display latent viral infection. KS tumorigenesis requires ongoing lytic viral replication as well, however, for reasons that are unclear but have been suggested to involve the production of angiogenic or mitogenic factors by lytically infected cells. Here we demonstrate that proliferating cells infected with KSHV in vitro display a marked propensity to segregate latent viral genomes, with only a variable but small subpopulation being capable of stable episome maintenance. Stable maintenance is not due to the enhanced production of viral or host trans-acting factors, but is associated with cis-acting, epigenetic changes in the viral chromosome. These results indicate that acquisition of stable KSHV latency is a multistep process that proceeds with varying degrees of efficiency in different cell types. They also suggest an additional role for lytic replication in sustaining KS tumorigenesis: namely, the recruitment of new cells to latency to replace those that have segregated the viral episome.
CARRIERS OF THE PATHOGENIC AMEBAS OF DYSENTERY
Journal: JAMA (1921)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
A feasibility trial of geriatric assessment and integrated care plan for older cancer patients.
Authors: Martine Puts, Schroder Sattar, Mary Ellen Macdonald, Michael Kulik, Kara McWatters, Katharine Lee, Eitan Amir, Raymond Woo-Jun Jang, Monika K. Krzyzanowska, Anthony M. Joshua, Johanne Monette, Doreen Wan-Chow-Wah, Shabbir M.H. Alibhai
Journal: Journal of Clinical Oncology (2016)

10054 Background: The majority of persons diagnosed with cancer are older adults. A comprehensive geriatric assessment (CGA) can identify current health issues and recommend interventions to decrease adverse outcomes and optimize the functional status and well-being of older adults. However, there is limited and conflicting evidence regarding the effectiveness of CGA in oncology settings. Here, we explore the impact of a CGA and integrated care plan in optimizing outcomes in older patients with advanced breast (BC), gastrointestinal (GI) or genitourinary (GU) cancers. Methods: A two-group parallel single-blind phase II RCT enrolled 60 patients aged 70 +, diagnosed with stage 2-4 GI, GU or BC, referred for chemotherapy or having received < 6 weeks of chemotherapy at Princess Margaret Cancer Centre. Patients need to be fluent in English, have a life expectancy > 6 months, ECOG PS 0-2 and able to provide informed consent. Randomization to intervention versus control group is 1:1 and stratified by treatment intent. The intervention includes a full CGA. Based on the CGA and discussion with the patient, tailored evidence-based interventions using a standardized intervention protocol were implemented. Participants in the intervention group are seen by the intervention team at baseline for the CGA and development of the integrated care plan; and at 3 and 6 months to assess intervention fidelity and measure outcomes. The co-primary outcomes are: 1) quality of life (QoL) (EORTC QLQ-C30); 2) modification of the cancer treatment plan. The secondary outcomes are: 1) functional status (OARS Instrumental Activities of Daily Living); and 2) feasibility of the study by tumor site. Results: 39 men and 21 women participated (response rate 63%). 13 Participants received adjuvant chemotherapy and 47 palliative chemotherapy. 33 Participants had GI, 14 GU and 13 BC. 12 participants died before 3 months. At three months, the mean change in global QOL from baseline was -6.9 points for the control group (mean score at baseline 63.7) and -2.0 points for the intervention group (mean score at baseline 66.7), resulting in a difference in mean change scores of 4.9 points. Conclusions: This study will inform the design of a phase 3 trial. Clinical trial information: NCT02222259.
A Randomized Clinical Trial of Cyclosporine in Cadaveric Renal Transplantation
Journal: New England Journal of Medicine (1986)

In a multicenter trial we investigated the effect of immunosuppressive therapy on graft and patient survival, renal function, and complications in 291 recipients of cadaveric renal transplants. One hundred forty-two patients were randomly assigned to treatment with cyclosporine and prednisone, and 149 to control immunosuppressive therapy (azathioprine and prednisone, with or without antilymphocyte globulin). At three years graft survival was 69 percent in the cyclosporine-treated patients and 58 percent in the controls (P = 0.05). The number of episodes of graft rejection was similar in the two groups, but the severity of rejection was significantly worse among the controls. Patient survival after three years was 90 percent in the cyclosporine group and 82 percent in the control group (P = 0.04). Acute tubular necrosis was an important risk factor for graft loss in both groups. Risk factors for death included diabetes and older age of the recipient. Renal function as indicated by the serum creatinine concentration or creatinine clearance was poorer in the cyclosporine-treated patients than in the controls, but has remained stable in both groups since the sixth month after transplantation. We conclude that, among recipients of cadaveric renal transplants, those treated with cyclosporine, despite having poorer (but stable) renal function, have better graft and patient survival at three years than those treated with alternative forms of immunosuppressive therapy. (N Engl J Med 1986; 314:1219–25.)
Abstract 4502: The role of A-to-I RNA editing in diversifying the microRNA functions in cancer
Authors: Han Liang
Journal: Cancer Research (2019)

Abstract Both miRNAs and A-to-I RNA editing, a widespread nucleotide modification mechanism, have recently emerged as key players in cancer pathophysiology. However, the functional impact of RNA editing of miRNAs in cancer remains largely unexplored. Here, we systematically characterized the miRNA editing profiles of ~9000 samples across 20 cancer types from miRNA sequencing data of The Cancer Genome Atlas and identified adenosine-to-inosine (A-to-I) RNA editing hotspots. Focusing on the RNA editing hotspot in miR-200b, a key tumor metastasis suppressor, we found that the miR-200b editing level correlates with patient prognosis opposite to that pattern for the wild-type miR-200b expression. We further experimentally showed that in contrast to wild-type miRNA, the edited miR-200b can promote cell invasion and migration through its impaired ability to inhibit ZEB1/ZEB2 and acquired concomitant ability to repress new targets including LIFR, a well-characterized metastasis suppressor. In another example, an ADAR2-catalyzed RNA editing site within the miR-379 is under-edited in tumors relative to normal tissues, with a high editing level being correlated with better patient survival times across cancer types. We demonstrate that in contrast to wild-type miRNA, edited miR-379 inhibited cell proliferation and promoted apoptosis in diverse tumor contexts in vitro. Importantly, through nanoliposomal delivery, edited miR-379 mimics significantly inhibited tumor growth and extended survival of mice. Our study indicates a role of RNA editing in diversifying miRNA function during cancer progression and highlights the translational potential of edited miRNAs as new class of cancer biomarkers and therapeutics. Citation Format: Han Liang. The role of A-to-I RNA editing in diversifying the microRNA functions in cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4502.
Massachusetts Medical Society
Authors: John Figgis Jewett, J. Ryder Neary, J. Allen Bryer, Nelson Portnoy, Knowles B. Lawrence, David W. Wallwork, Warren D. Babb, Allen G. Rice, Eugene Holden, William F. Hickey, Germain J. Bouchard, David C. Dow, John P. Ahearn, Solomon L. Skvirsky, Joseph P. Leone, Charles G. Shedd, Elwood O. Horne, Marshall A. Lamb
Journal: New England Journal of Medicine (1957)

COMMITTEE ON MATERNAL WELFAREMitral Stenosis, with Congestive Heart Failure and EndocarditisA twenty-eight-year-old gravida 1 visited a physician at four months of gestation but did not realize she was pregnant. There was no history of serious illness in the past, and she was working as a saleswoman.Besides an apparently normal intra-uterine pregnancy, physical examination showed the heart to be enlarged to the left, with a diastolic mitral murmur at the mid-sternum transmitted throughout the chest and an "aortic regurgitated murmur" that was "whistling" and was transmitted to the neck. There was no dyspnea, orthopnea or edema. The patient . . .
Diagnostic imaging in perspective
Authors: M. S. Potsaid
Journal: JAMA (1980)

RADIOLOGY was created by technology, has been nurtured by technology, and now is being put to the test by rapid technological advances. Increased application of sophisticated imaging systems has moved the specialty in a short time from the age of technology into the age of accountability. Radiology provides heretofore unheard-of diagnostic information, especially through the use of computers, which have revolutionized medical imaging. As radiologists perform internal physical examinations on patients, they visualize the human body in health and disease in ways never expected. While physicians desire to have the newer techniques available readily for their patients, the government desires even more strongly to limit their use to contain costs. The position of government is understandable, since money for health care has a limit, yet the demands for more and more funds continue, with diagnostic imaging receiving about 6% of the medical dollars.<sup>1</sup>Society cannot do all that is